Within the general framework of studies on the control of leukocyte proliferation and differentiation, specific investigations will attempt to: a) Further clarify the life history of immunocompetent lymphocytes in the rat, and their possible role in "surveillance" against neoplasia; b) Extend preliminary studies on subpopulations of B and T lymphocytes in normal and leukemic human blood; c) Further delineate the prognostic value of marrow chromosome studies in human "preleukemia." For the rat studies (a) in vivo labelling with tritiated thymidine will be combined with autoradiographic and cytogenetic studies on mixed lymphocyte cultures to test a proposed model for the life history of rat cells responsive to major histocompatibility antigens and their relationship to aging and neoplasia. For the studies of human B cells and T cells (b) the techniques will include kinetics in culture, cytogenetics, rosette formation, and immunofluorescence. Initially, attempts will be made to characterize the neoplastic clone in typical chronic lymphocytic leukemia. For human "preleukemia" (c) marrow chromosome findings will be correlated with the subsequent clinical course to determine the prognostic significance of marrow chromosome abnormalities in "preleukemic" states. BIBLIOGRAPHIC REFERENCES: Comparative Mitogenic Responses of Human lymphocytes to PHA and a Divalent Cation Ionophore. Jensen, P., Winger, L., Rasmussen, H., and Nowell, P. Am. J. Path. 82: 65a, 1976 (Abst). T Cell Variant of Chronic Lymphocytic Leukemia with Chromosome Abnormality and Defective Response to Mitogens. Nowell, P., Jensen, J., Winger, L., Daniele, R., and Growney, P. Brit. J. Haemat. 33:459-468, 1976.